Molecular biology of testicular germ cell tumors: Unique features awaiting clinical application

Testicular germ cell tumors (TGCTs) are the most common solid tumors in young adult men characterized by distinct biologic features and clinical behavior. Both genetic predispositions and environmental factors probably play a substantial role in their etiology. TGTCs arise from a malignant transformation of primordial germ cells in a process that starts prenatally, is often associated with a certain degree of gonadal dysgenesis, and involves the acquirement of several specific aberrations, including activation of SCF–CKIT, amplification of 12p with up-regulation of stem cell genes, and subsequent genetic and epigenetic alterations. Their embryonic and germ origin determines the unique sensitivity of TGCTs to platinum-based chemotherapy. Contrary to the vast majority of other malignancies, no molecular prognostic/predictive factors nor targeted therapy is available for patients with these tumors. This review summarizes the principal molecular characteristics of TGCTs that could represent a potential basis for development of novel diagnostic and treatment approaches.     

Pulmonary metastasectomy in germ cell tumors and prostate cancer

Pulmonary oligo-metastases and oligo-recurrences are terms used to define a set of clinical conditions consisting of limited metastatic malignant disease characterized by an intermediate aggressive behavior compared to diffuse metastatic conditions. If the primary tumor has been controlled and extra-thoracic lesions are excluded, there is a suggestion in the medical literature that removal of such lesions could potentially prolong survival. The lungs are a common metastatic spreading site, especially from epithelial malignancies and sarcomas; pulmonary surgical or interventional metastasectomy have been proposed with curative intent in case of limited tumor load (usually less than 5 lesions). There are many series reporting data about colorectal, renal or breast lung metastasectomy, but the absence of multi centric prospective trials determines a lack of definitive evidence, especially for less common tumors such as metastatic germ cell and prostate cancer. They rarely present in the oligo-metastatic form and their management is often based on personal experience. The aim of our article is to review the latest evidence in the treatment of pulmonary metastatic germ cell and prostate tumors. We cover the full range of treatments: from surgery to ablative radiotherapy and combination of local and systemic therapy. Despite the absence of evidence based guidelines, it emerges that pulmonary metastasectomy should always be considered when general criteria for resection have been met. In germ cell tumors surgery should be mainly reserved for residual disease after chemotherapy, whereas in prostate cancer, pulmonary metastasectomy should be preferred to avoid or delay hormonal deprivation therapy and its side effects.     

Heavy-chain immunoglobulin gene rearrangement and cytoplasmic immunoglobulin expression in acute monocytic leukemia following primary germ cell tumor

A case of acute monocytic leukemia with rearrangement of the immunoglobulin heavy-chain gene and strong cytoplasmic immunoglobulin expression in a young patient treated with multi-drug chemotherapy for primary seminomatous germ cell tumor 13 months earlier is reported. The short latency period from the beginning of therapy for primary germ cell tumor and the abrupt onset of leukemia with no identifiable prodrome bear similarities to podophyllotoxin-related leukemias.Supported by a grant from theFonds zur Förderung der wissen-schaftlichen Forschung (P09044-MED)     

Incidence of malignant ovarian germ cell tumors (MOGCTs) in Saudi Arabia

Incidence of malignant ovarian germ cell tumors (MOGCTs) in the Saudi Arabian population has not been studied before. Therefore, the primary objective of this study was to define the population-based incidence rates and histopathological types of MOGCTs in the Saudi Arabian population from 1999 to 2008. Our study showed that MOGCTs are a common type of ovarian tumors in the Saudi Arabian population, and the incidence rates and histopathological types are relatively comparable to the international populations with few differences.     

抑癌基因RASSF1启动子甲基化在肿瘤中的研究进展

肺癌和其它一些肿瘤中普遍存在人3号染色体短臂的杂合型丢失（loss of heterozygosity,LOH）,2000年Dammann等通过酵母双杂交技术从3p21.3分离鉴定出抑癌基因RASSF1A（rasassociation domain family 1A）。在许多人类肿瘤中存在RASSF1A启动子区域高甲基化,导致基因表观遗传失活。RASSF1A启动子区高甲基化可以作为肿瘤早期诊断和评价预后的一个候选分子标志。     

IQGAP2抑制结肠癌细胞侵袭且通过启动子异常甲基化致基因沉默

目的 探讨在结肠癌细胞系中,含IQ模序GTP酶激活蛋白(IQGAP)2的启动子甲基化状态及IQGAP2对结肠癌细胞侵袭的影响.方法 在人结肠癌RKO细胞株中,采用实时荧光定量聚合酶链反应(RT-PCR)、脱甲基化试剂5-aza-2'-deoxycytidine处理,甲基化特异性聚合酶链反应(MSP)法、甲基化测序检测I...     

Mobilization of CD34-positive tumour cells in a patient with testicular mixed germ cell tumour

Summary. Tumour cells from a patient with recurrent testicular germ cell cancer and bone marrow infiltration were found to express CD33 and CD34 in the absence of other haemopoiesis-associated antigens. After myelosup-pression and treatment with G-CSF for stem cell mobilization, CD34-positive tumour cells were detected in the peripheral blood in addition to normal haemopoietic progenitor cells. The tumour cells were decreased in the leukapheresis product. Retrospectively, the appearance of tumour cells in the peripheral blood after stem cell mobilization was the first indication of impending relapse.     

Successful treatment of radiotherapy and apatinib in patient with mediastinal mixed non-seminomatous germ cell tumor: A case report

Rationale:Mediastinal non-seminomatous germ cell tumors (MNSGCTs) are rare malignancies. Chemotherapy followed by surgical resection has been regarded as the standard management, but treatment options for chemotherapy-refractory patients or those with unresectable tumors are limited, resulting in a very poor prognosis.Patient concerns:An 18-year-old female presented with symptoms of cough, chest tightness, and shortness of breath for 2 months, and the symptoms gradually worsened.Diagnosis:Computed tomography (CT) revealed a large mediastinal mass invading the pericardium and great blood vessels. Serum human chorionic gonadotropin (HCG) and α-fetoprotein (AFP) levels were normal. Histopathological examination of biopsy specimens revealed mixed MNSGCT with embryonal carcinoma and immature teratoma components.Interventions:The patient achieved complete remission (CR) and long-term survival after multimodal therapy comprising chemotherapy, positron emission tomography/CT (PET/CT)-guided volumetric-modulated arc therapy (VMAT), and anti-angiogenic targeted therapy.Outcomes:The patient was followed up for more than 4 years without recurrence, metastasis, or treatment-related adverse effects.Lessons:The case presented here highlights the importance of multidisciplinary diagnosis and treatment, providing evidence that radiotherapy and anti-angiogenic therapy may play an important role in unresectable or residual tumors after failure of conventional treatments of MNSGCT. Percutaneous biopsy is necessary for diagnosis if the tumor is unresectable, and serum AFP and HCG levels are normal. Additionally, PET/CT is an effective method for evaluation of efficacy and radiotherapy guidance for patients with MNSGCTs.     

Huge right ventricular mass revealing a testicular nonseminomatous germ cell tumor

Background

Cardiac intracavitary metastases from a testicular cancer are very unusual, and intra-cardiac metastasis is exceptionally the first expression of a noncardiac primary neoplasm. We report a case of a young patient for whom a cardiac symptom led to the diagnosis of a metastatic testicular cancer.

High-dose chemotherapy with autologous stem cell support in poor-risk germ cell tumors

 High-dose chemotherapy (HDT) and stem cell transplantation is a newer treatment option widely applied in poor-risk germ cell tumor patients. Due to the increasing practical clinical experience and the availability of hematopoietic growth factors, this treatment approach has become a relatively safe procedure. Depending on the drugs used, the most prominent therapy-associated side effects are myelosuppression, infections, mucositis, moderate, mostly reversible neurotoxicity, and renal impairment. Because of their unique pharmacologic characteristics, carboplatin and etoposide have proved to be the most important drugs for HDT. It is not known whether the addition of ifosfamide or cyclophosphamide or other drugs to the combination of carboplatin and etoposide leads to superior results. It is not yet clear if HDT should already be instituted in first-line treatment of poor-risk patients, or later after relapse or incomplete response. Even if precise data on the therapeutic value of HDT are still missing because randomized trials are not yet ready for evaluation, there is good evidence for the effectiveness of HDT. The demonstration of remissions in cisplatin-refractory patients, the inversion of remission durations, and the induction of long-term freedom from disease in multiply relapsed patients who were deemed incurable with conventional-dose procedures argue in favor of HDT. Finally, the delineation of prognostic factors associated with a poor probability of survival after HDT contributes to the selection of patients who are likely to profit from HDT and those who should be spared from dose-intensive treatment. Received: 3 March 1998 / Accepted: 27 March 1998     

Metastasizing testicular germ-cell tumor with infiltration of the right heart: indication for primary metastasectomy

Cardiac intracavitary metastases are very uncommon. The case of a 42-year-old male patient with a testicular germ cell tumor extending into the superior caval vein, the left brachiocephalic vein, and the right heart, which manifested as a mild form of pulmonary embolization, is presented. Due to the perceived high risk of continuous embolization and the urgent need to begin systemic chemotherapy, a complete cardiac tumor resection was performed, utilizing a cardiopulmonary bypass, followed by a simultaneous orchiectomy. Histology revealed a 61-cm long vascular tumor as a metastasis of a yolk sac tumor originating from the left testis. There were no postoperative complications, and the patient is alive and without tumor recurrence 12 months after four cycles of systemic chemotherapy according to the PEB (cisplatin, etoposide, bleomycin) scheme. We conclude that in this special case aggressive surgical management following chemotherapy was very effective in controlling the disseminated testicular tumor.     

Recent developments in the management of testicular germ cell tumors

Testicular germ cell tumors are now generally regarded as a highly curable cancer in the majority of cases, even when patients present with advance disease. However that does not imply that researchers and clinicians have become complacent in their efforts to improve our understanding and the treatment outcome of this disease. This is an overview of recent developments in the management of testis cancer.     

Primary mixed germ cell tumor of the liver with sarcomatous components

Germ cell tumor(GCT)of the liver is extremely rare. Here,we describe a case of hepatic mixed GCT with significant sarcomatous components and elevated serum α-fetoprotein(AFP)in a 34-year-old man.Histopathologically,the tumor was composed of two GCTs components:yolk sac tumor and immature teratoma.The predominant components of immature teratoma consisted of several types of tissue that represented different germinal layers(endoderm,mesoderm and ectoderm) and showed varying degrees of differentiation with sig...     

抑癌基因ppENK甲基化在胰腺癌发病机制中的作用

目的 检测胰腺组织ppENK基因甲基化状态,探讨ppENK基因甲基化在胰腺癌发生发展过程中的作用.方法 采用甲基化特异性PCR(MSP)法检测胰腺癌组织、胰腺癌细胞株、正常胰腺组织中ppENK基因甲基化状态,分析其与临床病理特征的关系.RT-PCR法检测组织及细胞ppENKmRNA表达.应用去甲基化药物5-氮杂-2’-脱氧胞苷(5-Aza-dC)处理胰腺癌细胞株(PANC1、AsPC1),采用四甲基偶氮唑蓝(MTT)法检测细胞的增殖,流式细胞仪检测细胞凋亡及细胞周期,蛋白质印迹法检测DNA甲基转移酶3a(DNMT3a)蛋白表达.结果 正常胰腺组织表达ppENK mRNA,基因非甲基化.胰腺癌组织ppENK基因甲基化率为90.3％ (28/31),ppENK基因甲基化与临床病理特征无相关性.SW1990、PANC1、PC3、AsPC1、PuPan-1胰腺癌细胞株均无ppENK mRNA表达,基因均表现为甲基化,ppENK mRNA表达与其甲基化呈负相关.5-Aza-dC处理后,PANC1、AsPC1细胞的ppENK基因被去甲基化,ppENK mRNA恢复表达;细胞的增殖呈浓度依赖性被抑制;细胞凋亡率增加[(31.57±6.76)％比(3.21±1.43)％,P=0.002,( 16.6±8.22)％比(3.82±1.71)％,P=0.058];DNMT3a表达减少;PANC1的G1期细胞比例显著增加[(67.87±2.72)％比(54.57±7.18)％,P=0.040],S期细胞比例显著减少[(22.37±4.31)％比(33.73±4.63)％,P=0.036],AsPC1的G1期、S期细胞比例无明显变化(P =0.236、0.075).结论 ppENK基因甲基化是引起ppENK表达抑制的重要分子事件.ppENK基因去甲基化后可抑制胰腺癌细胞增殖,促进凋亡,细胞周期被阻滞在G1期,DNMT3a蛋白表达减少.     

肿瘤标志物在食管鳞状细胞癌中的研究与应用

食管鳞状细胞癌作为食管癌的主要类型, 是人类最常见的消化系恶性肿瘤之一. 作为诊断手段之一的肿瘤标志物检测, 具有简便、经济、快速、无创的特点, 更重要的是一些标志物在组织器官发生形态学变化之前就有表达, 因此, 肿瘤标志物对食管癌的研究就更有意义.本文综述近几年来一些发现和检测到的肿瘤标志物在食管鳞状细胞癌中的差异表达, 分别从基因、蛋白、自身免疫抗体、抗原及预测因子角度总结介绍.     

卵巢癌细胞卡铂耐药相关肿瘤抑制基因的表达变化及其启动子区甲基化观察

目的观察卵巢癌卡铂耐药相关肿瘤抑制基因的表达变化及其启动子区甲基化状态。方法应用分子生物信息学方法,从卵巢癌卡铂耐药基因表达谱芯片中筛选13个肿瘤抑制基因（VHL、COPS2、NOL7、GGNBP2、RBL1、S100A2、PARG1、PERP、TCF3、DNAJA3、ING1、RARRES3、RBBP8）,并采用RT-PCR法检测这些基因在卵巢癌卡铂耐药细胞系（SKOV3-CB）及其亲本细胞系（SKOV3）的表达;分析肿瘤抑制基因启动子区CPG岛并设计出8个基因（VHL、COPS2、NOL7、RBL1、PARG1、PERP、DNAJA3）的引物,采用甲基化特异性PCR法检测SKOV3-CB、SK-OV3细胞8个基因启动子区甲基化状态。结果与SKOV3相比,除GGNBP2基因外,其余12个基因均在SKOV3-CB中表达下调。SKOV3-CB、SKOV3的ING1、DNAJA3、VHL甲基化引物均能够扩增出产物,未甲基化引物均不能扩增出产物;COPS2、PERP甲基化引物均不能够扩增出产物,未甲基化引物均能够扩增出产物;PARG1、NOL7、RBL1甲基化引物与未甲基化引物均能够扩增出产物。结论卵巢癌卡铂耐药相关肿瘤抑制基因表达下调,其启动子区无甲基化;甲基化机制与卵巢癌卡铂耐药相关肿瘤抑制基因的表达下调无关。